The environment is increasingly being recognized for the role it might play in the global spread of clinically relevant antibiotic resistance. Environmental regulators monitor and control many of the ...pathways responsible for the release of resistance-driving chemicals into the environment (e.g., antimicrobials, metals, and biocides). Hence, environmental regulators should be contributing significantly to the development of global and national antimicrobial resistance (AMR) action plans. It is argued that the lack of environment-facing mitigation actions included in existing AMR action plans is likely a function of our poor fundamental understanding of many of the key issues. Here, we aim to present the problem with AMR in the environment through the lens of an environmental regulator, using the Environment Agency (England's regulator) as an example from which parallels can be drawn globally. The issues that are pertinent to environmental regulators are drawn out to answer: What are the drivers and pathways of AMR? How do these relate to the normal work, powers and duties of environmental regulators? What are the knowledge gaps that hinder the delivery of environmental protection from AMR? We offer several thought experiments for how different mitigation strategies might proceed. We conclude that: (1) AMR Action Plans do not tackle all the potentially relevant pathways and drivers of AMR in the environment; and (2) AMR Action Plans are deficient partly because the science to inform policy is lacking and this needs to be addressed.
This review focuses primarily on the beneficial effects for human health of exposure to ultraviolet radiation (UVR). UVR stimulates anti-inflammatory and immunosuppressive pathways in skin that ...modulate psoriasis, atopic dermatitis, and vitiligo; suppresses cutaneous lesions of graft-versus-host disease; and regulates some infection and vaccination outcomes. While polymorphic light eruption and the cutaneous photosensitivity of systemic lupus erythematosus are triggered by UVR, polymorphic light eruption also frequently benefits from UVR-induced immunomodulation. For systemic diseases such as multiple sclerosis, type 1 diabetes, asthma, schizophrenia, autism, and cardiovascular disease, any positive consequences of UVR exposure are more speculative, but could occur through the actions of UVR-induced regulatory cells and mediators, including 1,25-dihydroxy vitamin D
, interleukin-10, and nitric oxide. Reduced UVR exposure is a risk factor for the development of several inflammatory, allergic, and autoimmune conditions, including diseases initiated in early life. This suggests that UVR-induced molecules can regulate cell maturation in developing organs.
Background & Aims:
Altered mucosal glycosylation in inflammatory bowel disease and colon cancer could affect mucosal bacterial adherence. This study aimed to quantify and characterize ...mucosa-associated and intramucosal bacteria, particularly
Escherichia coli, in these conditions.
Methods:
Mucosa-associated bacteria were isolated, after dithiothreitol mucolysis, from biopsy samples obtained at colonoscopy (Crohn’s disease, n = 14 patients; ulcerative colitis, n = 21; noninflamed controls, n = 24) and at surgical resection (colon cancer, n = 21). Intramucosal bacteria were grown after gentamicin treatment followed by hypotonic lysis.
Results:
Mucosa-associated and intramucosal bacteria were cultured more commonly in Crohn’s disease (79%,
P = 0.03; and 71%,
P < 0.01, respectively), but not ulcerative colitis (38% and 48%), than in noninflamed controls (42% and 29%) and were commonly cultured from colon cancers (71% and 57%). Mucosa-associated
E. coli, which accounted for 53% of isolates, were more common in Crohn’s disease (6/14; 43%) than in noninflamed controls (4/24, 17%), as also were intramucosal
E. coli: Crohn’s disease, 29%; controls, 9%.
E. coli expressed hemagglutinins in 39% of Crohn’s cases and 38% of cancers but only 4% of controls, and this correlated (
P = 0.01) with adherence to the I407 and HT29 cell lines. Invasion was cell-line dependent.
E. coli, including nonadherent isolates, induced interleukin-8 release from the cell lines.
E. coli adhesins showed no blood group specificity, excepting 1 cancer isolate (HM44) with specificity for the Thomsen-Friedenreich antigen, but they could be blocked by soluble plantain fiber.
Conclusions:
These studies support a central role for mucosally adherent bacteria in the pathogenesis of Crohn’s disease and colon cancer. Soluble plant fibers that inhibit their adherence have therapeutic potential.
To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer.
Women with breast cancer enrolled in a breast ...cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes (
, and
). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons.
Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0%
3.5%;
< .001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in
or
The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for
and
, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for
and
.
A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.
Summary These guidelines for use of narrowband (TL‐01) ultraviolet B have been prepared for dermatologists by the British Photodermatology Group on behalf of the British Association of ...Dermatologists. They present evidence‐based guidance for treatment of patients with a variety of dermatoses and photodermatoses, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of background photobiology.
Background Although aggressive endoluminal therapy for superficial femoral artery (SFA) occlusive disease is commonplace, the implications of diabetes mellitus (DM) on long-term outcomes in this ...population are unclear. We examined the consequences of endovascular treatment of the SFA in patients with and without DM. Methods A database of patients undergoing endovascular treatment of the SFA between 1986 and 2005 was maintained. Three groups were defined: nondiabetic patients, those with non-insulin-dependent DM (NIDDM), and those with insulin-dependent DM (IDDM). Intention-to-treat analysis was performed. Results were standardized to TransAtlantic Inter-Society Consensus (TASC) and Society for Vascular Surgery criteria. Time-dependent outcomes were assessed with Kaplan-Meier survival analyses. Factor analyses were performed using a Cox proportional hazard model for time-dependent variables. Data are presented as mean ± SD where appropriate. Results Endovascular treatment (ie, balloon angioplasty ± adjuvant stenting in 38%) was initiated in 525 limbs in 437 patients (68% male; average age, 66 ± 14 years) for claudication failing conservative therapy or chronic critical limb ischemia (CLI). Of these, 50% were nondiabetic, 26% had NIDDM, and 24% had IDDM. Analyses were separated by those presenting with claudication (61%) and those presenting with CLI (39%). Among patients presenting with claudication, those with IDDM had significantly lower assisted primary patency ( P < .01) and a higher incidence of restenosis ( P = .04). Patencies at 3 years for nondiabetic, NIDDM, and IDDM were 62%, 72%, and 54% (primary), and 81%, 86%, and 65% (assisted primary), respectively. Patency and restenosis rates were associated with lesion calcification, TASC D lesion categorization, and acute periprocedural occlusion. Among patients presenting with CLI, patency and restenosis rates were equivalent across all groups; however, limb salvage was significantly worse for both groups of diabetic patients compared with nondiabetic (NIDDM, P = .01; IDDM, P = .02). Reduction in limb salvage rates was associated with presence of tissue loss at presentation, end-stage renal disease, and progression of distal disease on follow-up. Conclusions Endoluminal therapy for SFA occlusive disease yields lower assisted patency rates and higher restenosis rates for those patients presenting with claudication who have more advanced diabetes (ie, IDDM). Among those patients presenting with CLI, particularly those with tissue loss, limb salvage rates are lowered for the diabetic groups (NIDDM and IDDM) despite equivalent patency and restenosis rates.
Background: Mucosally adherent E. coli are found in inflammatory bowel disease (IBD) and colon cancer. They promote release of the proinflammatory cytokine interleukin‐8 (IL‐8). We explored ...mechanisms for this release and its inhibition by drugs.
Methods: IL‐8 release from colon epithelial cells in response to mucosal E. coli isolates from IBD, colon cancer, and controls was characterized at the cellular and molecular level.
Results: IL‐8 response of HT29 cells was greater with Crohn's disease (689 ± 298 mean ± SD pg IL‐8/mL at 4 hours, n = 7) and colon cancer isolates (532 ± 415 pg/mL, n = 14) than with ulcerative colitis (236 ± 58 pg/mL, n = 6) or control isolates (236 ± 100 pg/mL, n = 6, P < 0.0001). Bacterial supernatants contained shed flagellin that triggered IL‐8 release. For whole bacteria the IL‐8 response to E. coli that agglutinate red blood cells (548 ± 428 pg IL‐8/mL, n = 16), a function that correlates with epithelial invasion, was greater than for nonhemagglutinators (281 ± 253 pg/mL, n = 17; P < 0.0001). This was particularly marked among E. coli that, although flagellate, could not release IL‐8 from TLR5‐transfected HEK293 cells. IL‐8 release was mediated by extracellular‐regulated kinase (ERK) and p38 mitogen‐activated protein kinase (MAPK) and inhibited by mesalamine, but not hydrocortisone, at therapeutic concentrations.
Conclusions: Mucosa‐associated E. coli shed flagellin that elicits epithelial IL‐8 release but this may only become relevant when the mucosal barrier is weakened to expose basolateral TLR5. Adherent and invasive IBD and colon cancer E. coli isolates also elicit a flagellin‐independent IL‐8 response that may be relevant when the mucosal barrier is intact. The IL‐8 release is MAPK‐dependent and inhibited by mesalamine.
(Inflamm Bowel Dis 2007)
Adult drone honey bees from 4 Australian breeding lines were reared under similar conditions and examined for semen and sperm production when 14, 21 and 35 days old, during spring, summer and autumn. ...Almost half (40.5%) of all drones examined did not release any semen when manually everted. For those that released semen, the average volume released per drone was 1.09 μL (range 0.72 (±0.04)−1.12 (±0.04) μL) and the average number of sperms in the semen per drone was 3.63 × 10
6
(range 1.88 (±0.14)−4.11 (±0.17) × 10
6
). The release of semen was dependent on breeding line and age (
P
< 0.05), but not on the rearing season. The volume of semen released per drone was dependent on season, age, and breeding line (
P
< 0.05), while the concentration of sperm in the semen was dependent on season and breeding line (
P
< 0.05). Hence our data indicate that genetics underpins the maturation of drone honey bees as well as the volume of semen they release and the concentration of sperm in that semen.
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